New Treatments for Metastatic Prostate Cancer

Most cases of prostate cancer tend to be easily treated and curable, however, a subset of disease exists that does not respond to the traditional therapies of surgery, radiation therapy, cryotherapy, high intensity focused ultrasound or hormonal therapies. Hormonally resistant prostate cancer (HRPCA) - which is also commonly called castrate resistant prostate cancer (CRPC) - refers to prostate cancer that can either be newly diagnosed or recurrent after prior treatment and that continues to progress despite the elimination of testosterone with hormonal means. Nearly 45% of patients with this form of the disease usually will develop metastatic disease within two years.

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Over the last several years, a number of new drugs have been released offering great hope to the group of patients with resistant disease who develop metastases, who otherwise would not be able to be treated. These new drugs all work via different mechanisms. Perhaps in the not too distant future, combinations of these medications may prove to be helpful to provide prolonged survival in this previously challenging group of patients.

Provenge (Sipuleucel T) is the first immunotherapy that has been offered for the treatment of metastatic HRPCA. Patients who undergo treatment with this medication initially undergo leukapharesis, which is the harvesting of their own white blood then returning the remainder of the blood to the circulation. These white blood cells are then sent to a processing center and are cultured with a recombinant antigen that is specific to the prostate. After the Provenge is infused (three infusions over six weeks), there is an activation of T cells (a specific type of white blood cell that can attack the prostate cancer cells). This treatment is extremely well tolerated with the most common side effects being flu-like symptoms. The results of the phase 3 study for this medication demonstrated a reduction in the risk of death by 22.5% compared to a control group, increased 3 year survival by 38% compared to placebo, and extended median survival by 4.1 months compared to placebo.

Zytiga (Abiraterone) is another new medication that is used for patients who have metastatic castrate-resistant prostate cancer. These patients have received prior chemotherapy with docetaxel. In the upcoming months, it is anticipated that this medication will also receive an indication for patients who have not had prior treatment with docetaxel. Patients who use this medication also take a daily dose of prednisone. Zytiga works by interrupting the production of androgens at locations, such as the adrenal glands and the tumor itself, which are sites that are usually not addressed by hormonal ablation therapies. This results in decreasing levels of testosterone and other androgens that help the spread of the tumor. The results of the phase 3 trial with this drug demonstrated a 35% reduction in the risk of death and a 3.9 month difference in median overall survival

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Xtandi (Enzalutamide) is another recently-approved oral agent for patients with metastatic castrate-resistant prostate cancer who have received prior chemotherapy with docetaxel. It too will probably receive approval for usage without prior docetaxel administration. It works by targeting multiple steps in the production of androgen, including inhibiting androgen binding to an androgen receptor, inhibiting androgen receptor nuclear translocation, and by inhibiting androgen receptor interaction with DNA. This results in cell death, decreases the growth of cancer cells, and decreases the tumor volume. The phase 3 trial results have demonstrated a median overall survival of 18.4 months, 54% of patients reducing the PSA levels by 50% or more, an improvement in quality of life, an increase in time to PSA progression and an improvement in radiological evidence of progression free survival.

Besides these three recent advancements in the management of advanced prostate cancer, another agent - a radiopharmaceutical that targets the metastatic foci and increases overall survival - should also be released in the near future.